Thorough QT/QTc Study to Assess the Electrocardiographic Safety of a New Gadolinium-based Contrast Agent P03277 in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Guerbet
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Change-from-baseline Mean Effect of P03277 on QT Interval Expressed as QTc According to Fridericia's Formula (∆QTcF)
研究概览
简要总结
The study is a Phase I, Single center, Randomized, Cross-over Double-blind Placebo-controlled and Open-label Positive-controlled (moxifloxacin) in healthy volunteers.
The primary objective is to assess the cardiac safety after administration of P03277 to 48 healthy volunteers at dose of 0.1 mmol/kg (anticipated clinical dose) and 0.3 mmol/kg (supra-clinical dose) by evaluating the QT and QTc intervals.
详细描述
Each subjects will be administered with 4 products (P03277 at the 2 different doses, placebo and moxifloxacin) in a 4*4 cross over sequence balanced for first order carry over effect. Twelve subjects will be assigned to each sequence (6 males and 6 females). The volunteers will be enrolled sequentially by cohort of 8 subjects.
ECG measurements will be compared with ECG parameters collected after administration of placebo (Nacl 0.9%). The test sensitivity will be assessed using a positive control (moxifloxacin 400 mg per os) known to induce delays in QT intervals.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Diagnostic
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 59 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Subject assessed as healthy by a comprehensive clinical assessment (detailed medical history and complete physical examination)
- •Subject with a Body Mass Index (BMI) > 19 kg/m² and < 28 kg/m² and a weight at least of 40 kg for female and 50 kg for male and at maximum of 100 kg
排除标准
- 未提供
研究组 & 干预措施
Sequence 1
The sequence of administration is: P/ScD/PC/CD
Where:
- P = Placebo (Nacl 0.9%)
- CD = P03277 tested at 0.1 mmol/kg
- ScD = P03277 tested at 0.3 mmol/kg
- PC = Positive control (moxifloxacin 400 mg - per os).
干预措施: P03277 0.3 mmol/kg (Drug)
Sequence 1
The sequence of administration is: P/ScD/PC/CD
Where:
- P = Placebo (Nacl 0.9%)
- CD = P03277 tested at 0.1 mmol/kg
- ScD = P03277 tested at 0.3 mmol/kg
- PC = Positive control (moxifloxacin 400 mg - per os).
干预措施: P03277 0.1 mmol/kg (Drug)
Sequence 1
The sequence of administration is: P/ScD/PC/CD
Where:
- P = Placebo (Nacl 0.9%)
- CD = P03277 tested at 0.1 mmol/kg
- ScD = P03277 tested at 0.3 mmol/kg
- PC = Positive control (moxifloxacin 400 mg - per os).
干预措施: Moxifloxacin 400mg (Drug)
Sequence 1
The sequence of administration is: P/ScD/PC/CD
Where:
- P = Placebo (Nacl 0.9%)
- CD = P03277 tested at 0.1 mmol/kg
- ScD = P03277 tested at 0.3 mmol/kg
- PC = Positive control (moxifloxacin 400 mg - per os).
干预措施: NaCl 0.9% (Drug)
Sequence 2
The sequence of administration is: CD/PC/ScD/P
Where:
- P = Placebo (Nacl 0.9%)
- CD = P03277 tested at 0.1 mmol/kg
- ScD = P03277 tested at 0.3 mmol/kg
- PC = Positive control (moxifloxacin 400 mg - per os).
干预措施: P03277 0.1 mmol/kg (Drug)
Sequence 2
The sequence of administration is: CD/PC/ScD/P
Where:
- P = Placebo (Nacl 0.9%)
- CD = P03277 tested at 0.1 mmol/kg
- ScD = P03277 tested at 0.3 mmol/kg
- PC = Positive control (moxifloxacin 400 mg - per os).
干预措施: Moxifloxacin 400mg (Drug)
Sequence 2
The sequence of administration is: CD/PC/ScD/P
Where:
- P = Placebo (Nacl 0.9%)
- CD = P03277 tested at 0.1 mmol/kg
- ScD = P03277 tested at 0.3 mmol/kg
- PC = Positive control (moxifloxacin 400 mg - per os).
干预措施: NaCl 0.9% (Drug)
Sequence 2
The sequence of administration is: CD/PC/ScD/P
Where:
- P = Placebo (Nacl 0.9%)
- CD = P03277 tested at 0.1 mmol/kg
- ScD = P03277 tested at 0.3 mmol/kg
- PC = Positive control (moxifloxacin 400 mg - per os).
干预措施: P03277 0.3 mmol/kg (Drug)
Sequence 3
The sequence of administration is: ScD/CD/P/PC
Where:
- P = Placebo (Nacl 0.9%)
- CD = P03277 tested at 0.1 mmol/kg
- ScD = P03277 tested at 0.3 mmol/kg
- PC = Positive control (moxifloxacin 400 mg - per os).
干预措施: P03277 0.1 mmol/kg (Drug)
Sequence 3
The sequence of administration is: ScD/CD/P/PC
Where:
- P = Placebo (Nacl 0.9%)
- CD = P03277 tested at 0.1 mmol/kg
- ScD = P03277 tested at 0.3 mmol/kg
- PC = Positive control (moxifloxacin 400 mg - per os).
干预措施: Moxifloxacin 400mg (Drug)
Sequence 3
The sequence of administration is: ScD/CD/P/PC
Where:
- P = Placebo (Nacl 0.9%)
- CD = P03277 tested at 0.1 mmol/kg
- ScD = P03277 tested at 0.3 mmol/kg
- PC = Positive control (moxifloxacin 400 mg - per os).
干预措施: NaCl 0.9% (Drug)
Sequence 3
The sequence of administration is: ScD/CD/P/PC
Where:
- P = Placebo (Nacl 0.9%)
- CD = P03277 tested at 0.1 mmol/kg
- ScD = P03277 tested at 0.3 mmol/kg
- PC = Positive control (moxifloxacin 400 mg - per os).
干预措施: P03277 0.3 mmol/kg (Drug)
Sequence 4
The sequence of administration is: PC/P/CD/ScD
Where:
- P = Placebo (Nacl 0.9%)
- CD = P03277 tested at 0.1 mmol/kg
- ScD = P03277 tested at 0.3 mmol/kg
- PC = Positive control (moxifloxacin 400 mg - per os).
干预措施: P03277 0.1 mmol/kg (Drug)
Sequence 4
The sequence of administration is: PC/P/CD/ScD
Where:
- P = Placebo (Nacl 0.9%)
- CD = P03277 tested at 0.1 mmol/kg
- ScD = P03277 tested at 0.3 mmol/kg
- PC = Positive control (moxifloxacin 400 mg - per os).
干预措施: Moxifloxacin 400mg (Drug)
Sequence 4
The sequence of administration is: PC/P/CD/ScD
Where:
- P = Placebo (Nacl 0.9%)
- CD = P03277 tested at 0.1 mmol/kg
- ScD = P03277 tested at 0.3 mmol/kg
- PC = Positive control (moxifloxacin 400 mg - per os).
干预措施: NaCl 0.9% (Drug)
Sequence 4
The sequence of administration is: PC/P/CD/ScD
Where:
- P = Placebo (Nacl 0.9%)
- CD = P03277 tested at 0.1 mmol/kg
- ScD = P03277 tested at 0.3 mmol/kg
- PC = Positive control (moxifloxacin 400 mg - per os).
干预措施: P03277 0.3 mmol/kg (Drug)
结局指标
主要结局
Change-from-baseline Mean Effect of P03277 on QT Interval Expressed as QTc According to Fridericia's Formula (∆QTcF)
时间窗: from 1 hour before any administration until 24 hours post-administration at the following timepoints: -1 hour, 5 min, 10 min, 20 min, 30 min, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 8 hours, 24 hours.
Each subject was monitored with a 12-lead Holter electrocardiogram (ECG). The study had to show that both 0.1 and 0.3 mmol/kg doses of P03277 do not increase the QT interval corrected by Fridericia formula (QTcF). The study is successful if the difference between each of the two doses of P03277 and placebo for the largest mean change from baseline for the QTcF is lower than 10 milliseconds. The baseline was defined as the mean of the 3 triplicates ECG measured within 1 hour before each product administration.
次要结局
- Change-from-baseline Mean Effect of Moxifloxacin on QT Interval Expressed as QTc According to Fridericia's Formula (∆QTcF)(from 1 hour before any administration until 4 hours post-administration at the following timepoints: -1 hour, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours.)
- Predicted Value of ∆∆QTc at Cmax(from 1 hour before any administration until 24 hours post-administration.)